The per sex act probability of acquiring HIV infection is low but 2- to 10-fold higher in men who have sex with men compared to heterosexual transmission. Given the narrow genetic diversity of virus early in infection only a limited number of viruses in the infecting innoculum are fit to seed the new infection. Part of this fitness relates to matching inoculated viral trophisms to the HIV target cell in the vagina, rectum, or penis through established receptors such as DC-SIGN, CD4 and CCR-5. Heighten risk in the context of anal intercourse is undoubtedly associated with differences in target cell density and accessibility. Recent studies point to additional viral envelope characteristics in acute infection viruses such as shortened envelope variable loops and altered glycosylation patterns in subtype A and C viruses in heterosexual transmission, a pattern not observed in subtype B from men who have sex with men. These differences could result from subtype differences unrelated to transmission route or could be a result of selection pressure, making certain envelope patterns more fit for heterosexual versus homosexual transmission. To clarify whether these envelope motifs are linked to route of transmission the current proposal investigates subtype B viruses from acute/recent infection from an HIV heterosexual transmission cohort from Trinidad compared to subtype B viruses from recently infected homosexual men in Argentina. Examination of viral quasispecies at the time of infection and evolution of quasispecies as the virus adapts in the host 12 months after infection provide a means of understanding fine structural motifs of the envelope that contribute to successful transmission via heterosexual versus homosexual routes and the subsequent adaptation required for sustained infection. The study will use archived samples from two incident cohorts. Complete envelope sequences will be generated using extracted DNA from subject PBMC acquired at or before seroconversion in each of the cohorts and samples collected 1 year later in the Trinidad cohort. End-point dilution of template will be used to prevent bias in characterizing the viral population. The length and glycosylation of the variable loops of gp120 will be the primary focus of the comparison, but other relevant features of the envelope gene will also be examined.Project Narrative When HIV is sexually transmitted, only a few of the viruses actually get in to start a new infection;most of them are blocked. If we had a better understanding of how that happens, it would help a great deal in designing agents to block even further. This study examines the viruses in newly infected people to determine what they have in common that would provide a clue about why they gained entry while others did not.